Highlights
- •We found the splice-site mutation c.3244-2A>C results in aberrant transcripts.
- •The patient carrying c.3244-2A>C show more severe clinical manifestations.
- •These findings reveal important implications of aberrant transcripts in WD phenotype.
Abstract
This study aimed to identify aberrant transcripts of the new splice-site mutation
c.3244-2A>C in the Wilson disease (WD) gene (ATPase, Cu++ transporting, beta polypeptide,
ATP7B) and discuss its genotype and clinical phenotype. DNA and RNA were extracted
from peripheral blood lymphocytes, amplified by polymerase chain reaction (PCR) and
nested reverse transcription PCR (RT-nested PCR) to characterize the aberrant transcripts.
RT-nested PCR product sequencing comparison showed that c.3244-2A>C splice-site mutation
caused aberrant transcripts and formatted a new splice acceptor. Patient carrying
the splice-site mutation c.3244-2A>C presented early onset age, severe clinical manifestations,
and poor prognosis. WD patients with the splice-site mutation show severe clinical
manifestations, indicating that aberrant transcripts have important implications for
WD phenotype.
Graphical abstract
Graphical Abstract
Keywords
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References
- Diagnosing Wilson disease.Ann Intern Med. 1992; 117 ([PubMed:1596056]): 91
- Wilson's disease.Lancet. 2007; 369 ([PubMed:17276780]): 397-408
- Wilson disease.Gastroenterology. 2003; 125 ([PubMed:14724838]): 1868-1877
- Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.Nat Genet. 1993; 5 ([PubMed:8298640]): 338-343
- The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.Nat Genet. 1993; 5 ([PubMed:8298639]): 327-337
- The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.Nat Genet. 1993; 5 ([PubMed:8298641]): 344-350
- University of Alberta database.(Available at) ([accessed January 2010])
- Mutational analysis of ATP7B and genotype–phenotype correlation in Japanese with Wilson's disease.Hum Mutat. 2000; 15 ([PubMed:10790207]): 454-462
- Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease.Mol Genet Metab. 2005; 86 ([PubMed:15967699]): 277-285
- Association of ATP7B mutation detection rate with biochemical characteristics in Korean patients with Wilson disease.Ann Clin Lab Sci. 2010; 40 ([PubMed:20124325]): 15-19
- Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.J Hum Genet. 2011; 56 ([PubMed:21796144]): 660-665
- A novel RNA splicing mutation in Japanese patients with Wilson disease.Biochem Biophys Res Commun. 1995; 217 ([PubMed:8526905]): 16-20
- Abnormal RNA splicing resulting from consensus sequence splicing mutations of ATP7B.Hum Mutat. 2002; 20 ([PubMed:12325021]): 260-266
- RNA analysis of consensus splicing mutations. Implications for the diagnosis of Wilson disease.Genet Test Mol Biomarkers. 2009; 13 ([PubMed:19371217]): 185-191
- Feasibility of RNA studies on illegitimate transcription for molecular characterization of splicing mutations in the ATP7B gene: a case report.Mol Cell Probes. 2012; 26: 63-65
- Perspectives on Wilson's disease.Hepatology. 1990; 12 ([PubMed:2227823]): 1234-1239
- Guidelines for the diagnosis and treatment of hepatolenticular degeneration.Chin J Neurol. 2008; 8: 566-569
- Sequence variation database for the Wilson Disease copper transporter, ATP7B.Hum Mutat. 2007; 28 ([PubMed:17680703]): 1171-1177
- Wilson disease: identification of two novel mutations and clinical correlation in Eastern Chinese patients.World J Gastroenterol. 2007; 13 ([PubMed: 17876883]): 5147-5150
- The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis.Hepatology. 2004; 41 ([PubMed:15519648]): 758-763
- Genotype–phenotype correlation of patients with Wilson disease in Chinese population.Natl Med J China. 2003; 25 ([PubMed:12812649]): 309-411
- Molecular diagnosis of Wilson disease using prevalent mutations and informative single-nucleotide polymorphism markers.Clin Chem. 2007; 53 (PubMed:17634212): 1601-1608
- Mutation analysis of Wilson disease in the Spanish population-identification of a prevalent substitution and eight novel mutations in the ATP7B gene.Clin Genet. 2005; 68: 61-68
- Mutation analysis and the correlation between genotype and phenotype of Arg78Leu mutation in Chinese patients with Wilson disease.Arch Neurol. 2001; 58: 971-976
- Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.Clin Genet. 2005; 68: 524-532
- Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease.BMC Gastroenterol. 2010; 18: 10-18
- High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease.Scand J Gastroenterol. 2010; 45 ([PubMed:20491539]): 1232-1237
Article info
Publication history
Published online: July 21, 2014
Accepted:
July 14,
2014
Received in revised form:
June 14,
2014
Received:
April 22,
2014
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
